Document Type
Article
Publication Date
5-1-2026
Abstract
BACKGROUND: Numerous in vivo studies have demonstrated beta-2-adrenoceptor (β2AR) -agonism as permissive in the development of allergic lung inflammation, and have implicated the arrestin-dependent signaling arm of the β2AR in mediating this effect. However, the specific cell type(s) mediating β2AR regulation of allergic lung inflammation remain unestablished.
METHODS: To explore the potential contribution of airway epithelia in this phenomenon, we compared the ability of ractopamine (RP), recently identified as a Gs-biased beta-agonist, to that of the unbiased/balanced beta-agonist albuterol (ALB), on IL-13-stimulated mucin and cytokine production in human airway epithelia cultures in air-liquid interface (HAE).
RESULTS: ALB, which activates both the β2AR-arrestin and -Gs signaling pathways significantly augmented IL-13-induced mucin production in HAE. RP, which preferentially signals via Gs/PKA, did not. Although IL-13 stimulated production of numerous cytokines, including IL-1α, IL-1RA, MDC, TGF-α, and GROα, ALB-mediated augmentation of these cytokines was highly variable and not statistically significant. Similarly, RP did not augment the induction of cytokines stimulated by IL-13. Moreover, in contrast to previous studies that reported a requirement of concomitant β2AR agonism for IL-13 to stimulate cytokine production, such a requirement was observed only in minority of the (12) cultures examined.
CONCLUSIONS: These data implicate arrestin-dependent β2AR signaling augmenting airway epithelial mucin production as a contributor to the previously-demonstrated pro-inflammatory effects of β2AR agonism in vivo. Moreover, they suggest that beta-agonist effects on the cytokine profile in the allergen-inflamed lung may be influenced by specific asthmatic endotypes and involve cooperativity among multiple cell types.
Recommended Citation
Graumuller, Fred; Cervantes, Diana; Chan, Tung O.; Schaunaman, Niccolette; Villalba, Dominic R.; Dickey, Burton F.; Walker, Julia K. L.; Chu, Hong Wei; and Penn, Raymond B., "Qualitative Beta-2-Adrenoceptor Signaling in the Regulation of Human Airway Epithelia Mucin and Cytokine Production" (2026). Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers. Paper 62.
https://jdc.jefferson.edu/pulmcritcarefp/62
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
42067931
Language
English
Comments
This article is the author’s final published version in Respiratory Research, Volume 27, Issue 1, 2026, Article number 261.
The published version is available at https://doi.org/10.1186/s12931-026-03693-4. Copyright © The Author(s) 2026.